A Proposal to Make Biomedical Research into Alzheimer's Disease More Democratic Following an International Survey with Researchers

Abstract

Background: Therapeutic research into Alzheimer's disease (AD) has been dominated by the amyloid cascade hypothesis (ACH) since the 1990s. However, targeting amyloid in AD patients has not yet resulted in highly significant disease-modifying effects. Furthermore, other promising theories of AD etiology exist.

Objective: We sought to directly investigate whether the ACH still dominates the opinions of researchers working on AD and explore the implications of this question for future directions of research.

Methods: During 2019, we undertook an international survey promoted with the help of the Alzheimer's Association with questions on theories and treatments of AD. Further efforts to promote a similar study in 2021 did not recruit a significant number of participants.

Results: 173 researchers took part in the 2019 survey, 22% of which held "pro-ACH" opinions, tended to have more publications, were more likely to be male, and over 60. Thus, pro-ACH may now be a minority opinion in the field but is nevertheless the hypothesis on which the most clinical trials are based, suggestive of a representation bias. Popular vote of all 173 participants suggested that lifestyle treatments and anti-tau drugs were a source of more therapeutic optimism than anti-amyloid treatments.

Conclusion: We propose a more democratic research structure which increases the likelihood that promising theories are published and funded fairly, promotes a broader scientific view of AD, and reduces the larger community's dependence on a fragile economic model.

Keywords: Alzheimer’s disease; amyloid-β; dementia prevention; diversity in science; gender; lifestyle factors; lifestyle interventions; pharmaceutical industry; tau protein; women in science.

Fig. 1

A decision tree revealing pro-ACH/non-ACH differences according to the participant’s view on whether or not there is problematic adherence to the ACH. We cut the depth of the tree to 5. Leave nodes (i.e., the final node, colored in the figure) present the number of pro-ACH participants on the right and the number of non-ACH participants on the left. They are light blue to dark blue as a function of the proportion of non-ACH in the leave node, or they are light green to dark green as a function of the proportion of pro-ACH in the leave node. In the non-ACH group, 63 participants (47.37%) not identifying as male argue that there is problematic adherence to the ACH, compared to only 7 (18.42%) of the pro-ACH group with these characteristics. Conversely, on the other end of the scale, 6 males (or preferred not to say) of the pro-ACH group (15.79%) argued that there was no problematic adherence to the ACH and had more than 113 median publications. None of the non-ACH had this profile.